三七皂苷R1对血管紧张素Ⅱ诱导的小鼠血管平滑肌细胞增殖及AT1R/ MAPKs表达水平的影响

Effects of notoginsenoside R1 on AngⅡinduced proliferation of MOVAS cells and AT1R/MAPKs signaling pathway

【目的】探讨三七皂苷R1(NR1)对血管紧张素Ⅱ(AngⅡ)诱导的小鼠主动脉血管平滑肌细胞(MOVAS细胞)增殖及血管紧张素Ⅱ1型受体(AT1R)/丝裂原活化蛋白激酶(MAPKs)信号通路的影响。【方法】体外培养MOVAS细胞,予以AngⅡ诱导后,采用BrdU法检测细胞增殖。通过Western blot法检测细胞中AngⅡ中主要的2种受体AT1R、AT2R及MAPKs通路(ERK、p38、JNK)相关蛋白的表达变化。【结果】(1)AngⅡ(5μmol/L)可促MOVAS细胞增殖(P<0.01);NR1(50μmol/L)能够抑制AngⅡ诱导的MOVAS细胞增殖(P<0.01);对照组与NR1组比较,差异无统计学意义(P>0.05)。(2)与AngⅡ组相比,AngⅡ+NR1组中AT1R蛋白明显降低(P<0.05),而AT2R蛋白表达则无显著差异(P>0.05)。(3)NR1可显著抑制AngⅡ刺激后细胞内ERK、p38、JNK蛋白的磷酸化水平(P<0.01)。【结论】NR1可抑制AngⅡ诱导的MOVAS细胞增殖,其机制与下调AT1R进而抑制MAPKs的激活相关。

[Objective]To investigate the effects of notoginsenoside R1(NR1)on the proliferation of mice aortic smooth muscle cells(MOVAS cells)induced by angiotensinⅡ(AngⅡ)and the signal pathway of angiotensinⅡtype 1 receptor(AT1R)/mitogen activated protein kinases(MAPKs).[Methods]The proliferation of MOVAS cells was detected by BrdU method after AngⅡinduction.Western blot was used to detect the expression of the two main receptors of AngⅡ(AT1R and AT2R)and MAPKs pathway related proteins(ERK,p38,and JNK).[Results](1)AngⅡ(5μmol/L)could promote the proliferation of MOVAS cells(P<0.01).NR1(50μmol/L)could inhibit the proliferation of MOVAS cells induced by AngⅡ(P<0.01).There was no significant difference between control group and NR1 group(P>0.05).(2)Compared with AngⅡgroup,the expression of AT1R protein in AngⅡ+NR1 group was significantly lower(P<0.05),but there was no difference in the expression of AT2R protein(P>0.05).(3)NR1 could significantly inhibit the phosphorylation of ERK,p38 and JNK protein after AngⅡstimulation(P<0.01).[Conclusion]NR1 can inhibit the proliferation of MOVAS cells induced by AngⅡ,which may be related to down regulating AT1R and inhibiting the activation of MAPKs.